Microelectrode Biosensors for <i>in vivo</i> Analysis of Brain Interstitial Fluid

Chatard, Charles; Meiller, Anne; Marinesco, Stéphane

doi:10.1002/elan.201700836

Cited by 22 publications

(22 citation statements)

References 226 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite their potential imperfections, these methods offer an unparalleled opportunity to obtain extracellular fluid directly from tumor. Key observations can be validated with complementary methods, such as electrochemical probes used in neuroscience for the in vivo analysis of brain interstitial fluid (58). The biggest current limitation is the paucity of available data.…”

Section: Direct Sampling Of Tumor Interstitial Fluidmentioning

confidence: 99%

The Tumor Metabolic Microenvironment: Lessons from Lactate

2019

View full text Add to dashboard Cite

The extracellular milieu of tumors is generally assumed to be immunosuppressive due in part to metabolic factors. Here, we review methods for probing the tumor metabolic microenvironment. In parallel, we consider the resulting available evidence, with a focus on lactate, which is the most strongly increased metabolite in bulk tumors. Limited microenvironment concentration measurements suggest depletion of glucose and modest accumulation of lactate (less than 2-fold). Isotope tracer measurements show rapid lactate exchange between the tumor and circulation. Such exchange is catalyzed by MCT transporters, which cotransport lactate and protons (H þ). Rapid lactate exchange seems at odds with tumor lactate accumulation. We propose a potential resolution to this paradox. Because of the high pH of tumor cells relative to the microenvironment, H þ-coupled transport by MCTs tends to drive lactate from the interstitium into tumor cells. Accordingly, lactate may accumulate preferentially in tumor cells, not the microenvironment. Thus, although they are likely subject to other immunosuppressive metabolic factors, tumor immune cells may not experience a high lactate environment. The lack of clarity regarding microenvironmental lactate highlights the general need for careful metabolite measurements in the tumor extracellular milieu.

show abstract

Section: Direct Sampling Of Tumor Interstitial Fluidmentioning

confidence: 99%

The Tumor Metabolic Microenvironment: Lessons from Lactate

2019

View full text Add to dashboard Cite

show abstract

“…Electrochemical analysis has the advantages of easily created probes (being an inexpensive process), the ability to miniaturize the probes, and real-time measurement [1]. In addition, biosensors can be constructed with high selectivity, sensitivity, and time resolution using enzymatic reactions [2][3][4][5]. Biosensors then can be optimized according to its purpose (e.g., food, medical, industrial, or environmental analysis use).…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Oxidation of Amines Using a Nitroxyl Radical Catalyst and the Electroanalysis of Lidocaine

et al. 2018

View full text Add to dashboard Cite

The nitroxyl radical of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) can electro-oxidize not only alcohols but also amines. However, TEMPO has low activity in a neutral aqueous solution due to the large steric hindrance around the nitroxyl radical, which is the active site. Therefore, nortropine N-oxyl (NNO) was synthesized to improve the catalytic ability of TEMPO and to investigate the electrolytic oxidation effect on amines from anodic current changes. Ethylamine, diethylamine, triethylamine, tetraethylamine, isopropylamine, and tert-butylamine were investigated. The results indicated that TEMPO produced no response current for any of the amines under physiological conditions; however, NNO did function as an electrolytic oxidation catalyst for diethylamine, triethylamine, and isopropylamine. The anodic current depended on amine concentration, which suggests that NNO can be used as an electrochemical sensor for amine compounds. In addition, electrochemical detection of lidocaine, a local anesthetic containing a tertiary amine structure, was demonstrated using NNO with a calibration curve of 0.1-10 mM.around the nitroxyl radical active site, and an adequate response current could not be obtained under physiological conditions. Iwabuchi and colleagues [22] reported that 2-azaadamantane N-oxyl (AZADO), which lacks steric hindrance around the active site, exhibited greater activity than TEMPO in organic synthesis reactions. Less-hindered nitroxyl radicals with various steric environments have been synthesized, and those with less bulky functionality exhibited greater activity [23][24][25][26]. Therefore, nortropine N-oxyl (NNO), which was modeled on AZADO, was synthesized in one step as a novel nitroxyl radical compound [27]. The NNO was capable of electrolytic oxidation of alcohols in neutral aqueous solutions. The NNO could be used in place of enzymes, allowing non-enzymatic analysis of glucose under physiological conditions [27]. Phenylboronic acid derivatives have been investigated as glucose sensors [28][29][30]. Phenylboronic acid (PBA) spontaneously binds with a moiety containing a diol [31]. The structural and electrical changes in PBA derivative probes when PBA bonds with the diol moiety can be used for glucose detection [32][33][34]. However, these probes had low specificity for glucose and did not respond under physiological conditions. Superiority of NNO was demonstrated from this report [27]. In contrast, TEMPO has catalytic oxidation ability toward amines as well as alcohols [35][36][37]. Therefore, the present study examined the electrolytic oxidation effect of NNO on amines under physiological conditions and compared the results with those obtained with TEMPO. The results demonstrated that NNO was a good electrochemical analysis probe for secondary and tertiary amines and for isopropylamine under physiological conditions (Figure 1). The oxoammonium ion, which is the active species, reacts with the amine to form hydroxylamine. The catalyst regenerates by reoxidation of hydroxylamine. Furthermore, ele...

show abstract

“…Importantly, our conclusions can probably be generalized to other oxidase-based biosensors that have been used to measure neurotransmitters or metabolically-relevant molecules in the brain (Chatard et al, 2018;Dixon et al, 2002;Hascup et al, 2013;McMahon et al, 2007). The exact extent of phasic and tonic O 2 dependence would depend on the particular enzyme kinetics and on the basal extracellular concentrations of analyte relative to the magnitude of changes in the brain.…”

Section: Resultsmentioning

confidence: 77%

“…Phasic biosensor responses during locomotion bouts correlate with oxygen 1 transients 2 TACO sensor offers the opportunity to study cholinergic activity with unprecedented spatial 3 resolution and selectivity in behaving animals. However, since O 2 is a co-substrate of oxidases, 4 sensitivity to physiological O 2 variations is a potential issue of this type of biosensors (Baker et al, 5 2015;Chatard et al, 2018;Dixon et al, 2002;McMahon et al, 2007;Santos et al, 2015). To control 6…”

Section: Resultsmentioning

confidence: 99%

Phasic oxygen dynamics underlies fast choline-sensitive biosensor signals in the brain of behaving rodents

Santos

Sirota

2020

Preprint

View full text Add to dashboard Cite

Fast time-scale modulation of synaptic and cellular physiology by acetylcholine is critical for many cognitive functions, but direct local measurement of neuromodulator dynamics in freely-moving behaving animals is technically challenging. Recent in vivo brain measurements using choline oxidase (ChOx)-based electrochemical biosensors have reported surprising fast cholinergic transients associated with reward-related behavioral events. However, in vivo recordings with conventional ChOx biosensors could be biased by phasic local field potential and O2-evoked enzymatic responses. Here, we have developed a Tetrode-based Amperometric ChOx (TACO) sensor enabling minimally invasive artifact-free simultaneous measurement of cholinergic activity and O2. Strikingly, the TACO sensor revealed highly-correlated O2 and ChOx transients following spontaneous locomotion and sharp-wave/ripples fluctuations in the hippocampus of behaving rodents. Quantitative analysis of spontaneous activity, in vivo and in vitro exogenous O2 perturbations revealed a directional effect of O2 on ChOx phasic signals. Mathematical modeling of biosensors identified O2-evoked non-steadystate ChOx kinetics as a mechanism underlying artifactual biosensor phasic transients. This phasic O2-dependence of ChOx-based biosensor measurements confounds phasic cholinergic dynamics readout in vivo, challenging previously proposed ACh role in reward-related learning. The discovered mechanism and quantitative modeling is generalizable to any oxidase-based biosensor, entailing rigorous controls and new biosensor designs.

show abstract

Microelectrode Biosensors for in vivo Analysis of Brain Interstitial Fluid

Cited by 22 publications

References 226 publications

The Tumor Metabolic Microenvironment: Lessons from Lactate

The Tumor Metabolic Microenvironment: Lessons from Lactate

Electrochemical Oxidation of Amines Using a Nitroxyl Radical Catalyst and the Electroanalysis of Lidocaine

Phasic oxygen dynamics underlies fast choline-sensitive biosensor signals in the brain of behaving rodents

Contact Info

Product

Resources

About